BENZAZEPINONE CALCIUM-CHANNEL BLOCKERS .2. STRUCTURE-ACTIVITY AND DRUG-METABOLISM STUDIES LEADING TO POTENT ANTIHYPERTENSIVE AGENTS - COMPARISON WITH BENZOTHIAZEPINONES

被引：65
作者：
FLOYD, DM
KIMBALL, SD
KRAPCHO, J
DAS, J
TURK, CF
MOQUIN, RV
LAGO, MW
DUFF, KJ
LEE, VG
WHITE, RE
RIDGEWELL, RE
MORELAND, S
BRITTAIN, RJ
NORMANDIN, DE
HEDBERG, SA
CUCINOTTA, GG
机构：
[1] Bristol-Myers Squibb Pharmaceutical Research Institute, New Jersey 08543-4000, P.O. Box 4000, Princeton
来源：
JOURNAL OF MEDICINAL CHEMISTRY | 1992年 / 35卷 / 04期
关键词：
D O I：
10.1021/jm00082a018
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
As part of a program to discover potent antihypertensive analogues of diltiazem (3a), we prepared 1-benzazepin-2-ones (4). Benzazepinones competitively displace radiolabeled diltiazem, and show the same absolute stereochemical preferences at the calcium channel receptor protein. Derivatives of 4 containing a trifluoromethyl substituent in the fused aromatic ring show potent and long-acting antihypertensive activity. Studies of the metabolism of 4 lead to the metabolically stable antihypertensive calcium channel blockers 5a and 5c. Benzazepinone 5a is a longer acting and more potent antihypertensive agent than the second generation diltiazem analogue TA-3090 (3e).
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页码：756 / 772
页数：17
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